A direct tissue-grafting approach to increasing endogenous brown fat

Nicole R. Blumenfeld, Hwan June Kang, Anna Fenzl, Ziwei Song, Janice J. Chung, Ranjodh Singh, Roshawn Johnson, Ayse Karakecili, Jun B. Feranil, Ninna S. Rossen, Vivian Zhang, Sahir Jaggi, Bret McCarty, Steven Bessler, Gary J. Schwartz, Robert Grant, Judith Korner, Florian W. Kiefer, Brian M. Gillette, Samuel K. Sia

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4 Scopus citations

Abstract

There is widespread evidence that increasing functional mass of brown adipose tissue (BAT) via browning of white adipose tissue (WAT) could potentially counter obesity and diabetes. However, most current approaches focus on administration of pharmacological compounds which expose patients to highly undesirable side effects. Here, we describe a simple and direct tissue-grafting approach to increase BAT mass through ex vivo browning of subcutaneous WAT, followed by re-implantation into the host; this cell-therapy approach could potentially act synergistically with existing pharmacological approaches. With this process, entitled "exBAT", we identified conditions, in both mouse and human tissue, that convert whole fragments of WAT to BAT via a single step and without unwanted off-target pharmacological effects. We show that ex vivo, exBAT exhibited UCP1 immunostaining, lipid droplet formation, and mitochondrial metabolic activity consistent with native BAT. In mice, exBAT exhibited a highly durable phenotype for at least 8 weeks. Overall, these results enable a simple and scalable tissue-grafting strategy, rather than pharmacological approaches, for increasing endogenous BAT and studying its effect on host weight and metabolism.

Original languageEnglish (US)
Article number7957
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

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    Blumenfeld, N. R., Kang, H. J., Fenzl, A., Song, Z., Chung, J. J., Singh, R., Johnson, R., Karakecili, A., Feranil, J. B., Rossen, N. S., Zhang, V., Jaggi, S., McCarty, B., Bessler, S., Schwartz, G. J., Grant, R., Korner, J., Kiefer, F. W., Gillette, B. M., & Sia, S. K. (2018). A direct tissue-grafting approach to increasing endogenous brown fat. Scientific reports, 8(1), [7957]. https://doi.org/10.1038/s41598-018-25866-y